Efficacy of topical brimonidine-timolol for haemangioma of infancy and perils of off-label prescribing

Abstract

We report three patients with superficial haemangiomas treated topically with Combigan ophthalmic solution (brimonidine 0.2%–timolol 0.5%), a combination selective α-2-adrenergic agonist and non-selective β-blocker Food and Drug Administration-approved for use in glaucoma. Topical brimonidine 0.2%-timolol 0.5% therapy improved the appearance of haemangiomas in all the cases. Two patients did not experience any adverse effects. One patient had hypothermic episodes which were initially thought to be because of brimonidine 0.2%-timolol 0.5% therapy. However, an episode occurred a few weeks after discontinuation and brimonidine 0.2%-timolol 0.5% therapy was ruled out as a cause. Despite the benefit, off-label use of brimonidine 0.2%-timolol 0.5% therapy served as a pitfall in the evaluation of an unusual constellation of worrisome symptoms. In conclusion, brimonidine 0.2%-timolol 0.5% therapy is a promising alternative in the topical treatment of haemangiomas. It may have synergistic effects and increased efficacy by targeting haemangiomas via two mechanisms (α-agonism and β-inhibition), but the risk of unforeseen adverse effects must always be considered when prescribing off-label treatment, especially in infants.

Review of topical beta blockers as treatment for infantile hemangiomas

“…In the third case, treatment was stopped prematurely as the child suffered hypothermic episodes that were later found to be associated with duloxetine excreted in breast milk (10) . Brimonidine exerts an alpha-2 adrenergic effect on normal vasculature and was therefore thought to have a synergistic effect to timolol.…”

The Role of Topical Timolol in the Treatment of Infantile Hemangiomas: A Systematic Review and Meta-analysis

“…Sleep disturbance was the only systemic adverse effect reported in two cases (23,42). Rebound growth occurred in 4 patients from 3 studies (27,32,46). In 3 patients treatment was restarted, still leading to complete resolution of the IH (32,46).…”

Adverse Events in Young and Preterm Infants Receiving Topical Timolol for Infantile Hemangioma

“…Hypothermia has been reported in younger infants, as was observed in our patient 2 . One case of hypothermia has been reported with topical application of brimonidine–timolol for the treatment of IHs .…”